Signal transduction in LPS-activated aged and young monocytes

Aged monocytes, that is, monocytes purified from the blood of donors greater than or equal to 65 years of age, when compared with young monocytes, that is, monocytes purified from the blood of young donors 25 years of age, display a decrease in interleukin-6 (IL-6) and tumor necrosis factor (TNF) production after activation by lipopolysaccharide (LPS). The LPS concentration required to obtain IL-6 and TNF production is much higher for aged monocytes than for young monocytes, Furthermore, the intensity of TNF and IL-6 production was much weaker for LPS-activated aged monocytes than for LPS-activated young monocytes, In addition, deficient protein kinase C (PKC)-alpha, PKC-beta I, and PKC-beta II activation, deficient mitogen-activated protein kinase (MAP-Kinase) activation, and deficient expression of c-Fos and c-Jun was observed in LPS-activated aged monocytes when compared with LPS-activated young monocytes, These data suggest that age induces human monocyte immune deficiencies that could be observed not only at the functional level but also in the signal transduction pathways.